A permissive environment for HIV-1 replication has been identified. In tissue culture, this environment is generated by two cell types that are derived from skin: dendritic cells and memory T lymphocytes. The two cells emigrate from thin sheets of cultured skin and form conjugates with one another. When any of >20 viral isolates are applied, rapid HIV-1 replication takes place, in the absence of any added stimuli. The infection is initiated by small numbers of infected dendritic cells, but T cell contact is essential. During infection, the interacting dendritic cells and T cells fuse to form syncytia; in these syncytia two factors that drive HIV-1 transcription are found -- NF-kB from the dendritic cells and Sp1 via the T cells. This milieu for HIV-1 replication very likely takes place in vivo. The first example involves the surface of the adenoid and tonsil. This surface is a "lymphoepithelium" in which T cells and activated dendritic cells are numerous. In tissues taken from asymptomatic HIV-1 infected individuals, many HIV-1 infected cells were found within and just beneath the lymphoepithelium. These cells were for the most part syncytia and carried the markers of dendritic cells. Another site where activated dendritic cells and memory T cells are normally found is afferent lymph, where the cells are migrating from tissues to draining lymphoid organs and are known to form conjugates with one another. If infected, these conjugates would represent a chronic environment for HIV-1 replication in the absence of standard antigenic stimuli. Dendritic cells and T cells are always trafficking in the afferent lymphatics throughout our bodies, delivering leukocytes into the lymph node, so if productively infected this could be an important feature of disease pathogenesis. To determine if these cells are infected and replicating virus in HIV-1 infected individuals, it is required to directly cannulate these lymphatics and analyze the cells and lymph fluid, comparing these to a simultaneous blood sample.